Abstract
Objective:To elucidate the degree of genetic polymorphisms CYP2C19 (CYP2C19*2, CYP2C19*3) of key drug metabolizing enzymes on the antiplatelet effect of clopidogrel response in patients with acute ischemic stroke from Saudi Arabia.Methods:A case-control study carried out at Neurology Clinics at Asser Central Hospital, Abha, Kingdom of Saudi Arabia from October 2015 to January 2016 and included 25 stroke patients responding to clopidogrel therapy and 25 stroke patients non responding to clopidogrel monotherapy. After obtaining their informed consent, the blood samples were collected and genotyped for CYP2C19 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP Method). Allele frequencies were derived from genotypic data and platelet aggregation was measured using multiple electrode aggregometry on the multiplate analyser. Chi Square tests, p-values, odds ratio (OR) and corresponding confidence intervals were calculated for each polymorphism.Results:The CYP2C19*2 (681G>A) and CYP2C19*3 (636 G>A) polymorphism were seen to be in Hardy–Weinberg equilibrium and showed significant allelic and genotypic association between responders and non-responders to clopidogrel (p<0.01). The CYP2C19*2: allelic chi-square=21.49, p=0.000036, OR=5.52 (2.42-12.83); Genotypic Chi-square=10.27, p=0.001, OR=7.88 (1.78-9.73). The CYP2C19*3: Allelic chi-square=11.66, p=0.0006, OR=3.45 (1.57-7.70); genotypic chi-square=4.37, p=0.036, OR=3.69 (0.90-5.81). The variant allele (homozygous and homozygous Mutant) showed significant influence on platelet inhibition and the antiplatelet effect of clopidogrel in ischemic stroke.Conclusion:Our findings provide certain evidence on the genetic effect of CYP2C19 on clopidogrel responsiveness in stroke patients from Saudi Arabia.
Highlights
أظهرت نتائج الدراسةبعض الدلالات على التأثير الوراثي لل:الخاتمة على الاستجابة كلوبيدوقرل عند مرضى السكتة الدماغيةCYP2C19
The CYP2C19*2 (681G>A) and CYP2C19*3 (636 G>A) polymorphism were seen to be in Hardy– Weinberg equilibrium and showed significant allelic and genotypic association between responders and nonresponders to clopidogrel (p
Alhazzani et al Stroke is a major cause of adult neurological disability and mortality
Summary
Group one comprised 25 stroke patients that were non- responders to clopidogrel therapy. Group 2 comprised 25 stroke patients that were responders to clopidogrel therapy. Subjects were included in the study they had received a 75 mg maintenance dose of clopidogrel at least 6 hours prior to blood sampling. Five ml blood sample, (2 ml in EDTA coated vials for DNA isolation, and 3 ml in plain tubes for serum separation for performing platelet aggregation study) were collected by single time venipuncture. Two ml of peripheral venous blood samples were obtained from subjects in a catheterization laboratory prior to the dose of clopidogrel. The association of ADP induced platelet aggregation level by CYP2C19*2,*3 polymorphisms in clopidogrel treated patients with ischemic stroke with genotypes was determined by Man Whitney U test, and p
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